Displaying publications 21 - 40 of 54635 in total

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  1. β-Thalassemias
    Thong MK, Ngim CF
    N Engl J Med, 2021 Jun 03;384(22):2165.
    PMID: 34077655 DOI: 10.1056/NEJMc2105064
    Matched MeSH terms: Humans
  2. Fulltext β-Caryophyllene Induces Apoptosis and Inhibits Angiogenesis in Colorectal Cancer Models
    Dahham SS, Tabana Y, Asif M, Ahmed M, Babu D, Hassan LE, et al.
    Int J Mol Sci, 2021 Sep 29;22(19).
    PMID: 34638895 DOI: 10.3390/ijms221910550
    Beta-Caryophyllene (BCP), a naturally occurring sesquiterpene abundantly found in cloves, hops, and cannabis, is the active candidate of a relatively new group of vascular-inhibiting compounds that aim to block existing tumor blood vessels. Previously, we have reported the anti-cancer properties of BCP by utilizing a series of in-vitro anti-tumor-related assays using human colorectal carcinoma cells. The present study aimed to investigate the effects of BCP on in-vitro, ex-vivo, and in-vivo models of anti-angiogenic assays and evaluate its anti-cancer activity in xenograft tumor (both ectopic and orthotopic) mice models of human colorectal cancer. Computational structural analysis and an apoptosis antibody array were also performed to understand the molecular players underlying this effect. BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF) secretion from human umbilical vein endothelial cells and sprouting of rat aorta microvessels. BCP has a probable binding at Site#0 on the surface of VEGFR2. Moreover, BCP significantly deformed the vascularization architecture compared to the negative control in a chick embryo chorioallantoic membrane assay. BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively. The histological analysis of the tumor from BCP-treated mice revealed a clear reduction of the density of vascularization. In addition, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions. These results suggest that BCP acts at multiple stages of angiogenesis and could be used as a promising therapeutic candidate to halt the growth of colorectal tumor cells.
    Matched MeSH terms: Humans
  3. α6-Containing GABAA Receptors: Functional Roles and Therapeutic Potentials
    Sieghart W, Chiou LC, Ernst M, Fabjan J, M Savić M, Lee MT
    Pharmacol Rev, 2022 Jan;74(1):238-270.
    PMID: 35017178 DOI: 10.1124/pharmrev.121.000293
    GABAA receptors containing the α6 subunit are highly expressed in cerebellar granule cells and less abundantly in many other neuronal and peripheral tissues. Here, we for the first time summarize their importance for the functions of the cerebellum and the nervous system. The cerebellum is not only involved in motor control but also in cognitive, emotional, and social behaviors. α6βγ2 GABAA receptors located at cerebellar Golgi cell/granule cell synapses enhance the precision of inputs required for cerebellar timing of motor activity and are thus involved in cognitive processing and adequate responses to our environment. Extrasynaptic α6βδ GABAA receptors regulate the amount of information entering the cerebellum by their tonic inhibition of granule cells, and their optimal functioning enhances input filtering or contrast. The complex roles of the cerebellum in multiple brain functions can be compromised by genetic or neurodevelopmental causes that lead to a hypofunction of cerebellar α6-containing GABAA receptors. Animal models mimicking neuropsychiatric phenotypes suggest that compounds selectively activating or positively modulating cerebellar α6-containing GABAA receptors can alleviate essential tremor and motor disturbances in Angelman and Down syndrome as well as impaired prepulse inhibition in neuropsychiatric disorders and reduce migraine and trigeminal-related pain via α6-containing GABAA receptors in trigeminal ganglia. Genetic studies in humans suggest an association of the human GABAA receptor α6 subunit gene with stress-associated disorders. Animal studies support this conclusion. Neuroimaging and post-mortem studies in humans further support an involvement of α6-containing GABAA receptors in various neuropsychiatric disorders, pointing to a broad therapeutic potential of drugs modulating α6-containing GABAA receptors. SIGNIFICANCE STATEMENT: α6-Containing GABAA receptors are abundantly expressed in cerebellar granule cells, but their pathophysiological roles are widely unknown, and they are thus out of the mainstream of GABAA receptor research. Anatomical and electrophysiological evidence indicates that these receptors have a crucial function in neuronal circuits of the cerebellum and the nervous system, and experimental, genetic, post-mortem, and pharmacological studies indicate that selective modulation of these receptors offers therapeutic prospects for a variety of neuropsychiatric disorders and for stress and its consequences.
    Matched MeSH terms: Humans
  4. α1-Acid Glycoprotein Has the Potential to Serve as a Biomimetic Drug Delivery Carrier for Anticancer Agents
    Matsusaka K, Ishima Y, Maeda H, Kinoshita R, Ichimizu S, Taguchi K, et al.
    J Pharm Sci, 2019 11;108(11):3592-3598.
    PMID: 31288036 DOI: 10.1016/j.xphs.2019.07.002
    Nanosize plasma proteins could be used as a biomimetic drug delivery system (DDS) for cancer treatment when loaded with anticancer drugs based on the fact that plasma proteins can serve as a source of nutrients for cancer cells. This prompted us to investigate the potential of α1-acid glycoprotein (AGP) for this role because it is a nanosize plasma protein and binds a variety of anticancer agents. Pharmacokinetic analyses indicated that AGP is distributed more extensively in tumor tissue than human serum albumin, which was already established as a cancer DDS carrier. AGP is possibly being incorporated into tumor cells via endocytosis pathways. Moreover, a synthetic AGP-derived peptide which possesses a high ability to form an α-helix, as deduced from the primary structure of AGP, was also taken up by the tumor cells. AGP loaded with anticancer agents, such as paclitaxel or nitric oxide, efficiently induced tumor cell death. These results suggest that AGP has the potential to be a novel DDS carrier for anticancer agents.
    Matched MeSH terms: Humans
  5. α-thalassemia-associated hydrops fetalis: A rare cause of thyrotoxic cardiomyopathy
    Tumian NR, Wong M, Wong CL
    J Obstet Gynaecol Res, 2015 Jun;41(6):967-70.
    PMID: 25510540 DOI: 10.1111/jog.12648
    α°-thalassemia is a well-known cause of hydrops fetalis in South-East Asia and can be detected in utero. We report a very rare case of thyrotoxic cardiomyopathy associated with hyperplacentosis secondary to α°-thalassemia-associated hydrops fetalis. A 22-year-old primigravida with microcytic anemia presented at 27 weeks' gestation with pre-eclampsia, hyperthyroidism and cardiac failure. Serum β-human chorionic gonadotrophin was markedly elevated and abdominal ultrasound revealed severe hydropic features and enlarged placenta. Serum β-human chorionic gonadotrophin, cardiac function and thyroid function tests normalized after she delivered a macerated stillbirth. Histopathology of the placenta showed hyperplacentosis. Blood DNA analysis revealed that both patient and husband have the α°-thalassemia trait. This case illustrates a very atypical presentation of α°-thalassemia-associated hydrops fetalis and the importance of early prenatal diagnosis of α-thalassemia in women of relevant ethnic origin with microcytic anemia so that appropriate genetic counseling can be provided to reduce maternal morbidity and the incidence of hydrops fetalis.
    Matched MeSH terms: Humans
  6. Fulltext α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis
    Zainal NZ, Alauddin H, Ahmad S, Hussin NH
    Malays J Pathol, 2014 Dec;36(3):207-11.
    PMID: 25500521
    Thalassaemia carriers are common in the Asian region including Malaysia. Asymptomatic patients can be undiagnosed until they present for their antenatal visits. Devastating obstetric outcome may further complicate the pregnancy if both parents are thalassaemia carriers leading to hydrophic fetus due to haemoglobin Bart's disease. However in certain cases where unexplained hydrops fetalis occur in parents with heterozygous thalassaemia carrier,mutated α genes should be suspected. We report a twenty-nine year old woman in her third pregnancy with two previous pregnancies complicated by early neonatal death at 21 and 28 weeks of gestation due to hydrops fetalis. DNA analysis revealed the patient to have heterozygous (--SEA) α-gene deletion, while her husband has a compound heterozygosity for α(3.7) deletion and codon 59 (GGC → GAC) mutation of the α-gene. This mutation, also known as hemoglobin Adana, can explain hydrops fetalis resulting from two alpha gene deletions from the patient (mother) and a single alpha gene deletion with mutation from the father. The third pregnancy resulted in a grossly normal baby boy with 3 α-gene deletions (HbH disease). We postulate that, in view of heterogenisity of the α-thalassaemia in this patient with severely unstable haemoglobin Adana chains from her husband, there will be a 25% possibility of fetal hydrops in every pregnancy.
    Matched MeSH terms: Humans
  7. Fulltext α-Mangostin from Cratoxylum arborescens demonstrates apoptogenesis in MCF-7 with regulation of NF-κB and Hsp70 protein modulation in vitro, and tumor reduction in vivo
    Ibrahim MY, Hashim NM, Mohan S, Abdulla MA, Kamalidehghan B, Ghaderian M, et al.
    Drug Des Devel Ther, 2014;8:1629-47.
    PMID: 25302018 DOI: 10.2147/DDDT.S66105
    Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 μg/mL, thereby indicating that AM has the attributes to induce cell death in tumor cells. The treatment of MCF-7 cells with AM prompted apoptosis with cell death-transducing signals. This regulated the mitochondrial membrane potential by down-regulation of Bcl-2 and up-regulation of Bax, thereby causing the release of cytochrome c from the mitochondria into the cytosol. The liberation of cytochrome c activated caspace-9, which, in turn, activated the downstream executioner caspace-3/7 with the cleaved poly (ADP-ribose) polymerase protein, thereby leading to apoptotic alterations. Increase of caspace 8 had showed the involvement of an extrinsic pathway. This type of apoptosis was suggested to occur through both extrinsic and intrinsic pathways and prevention of translocation of NF-κB from the cytoplasm to the nucleus. Our results revealed AM prompt apoptosis of MCF-7 cells through NF-κB, Bax/Bcl-2 and heat shock protein 70 modulation with the contribution of caspaces. Moreover, ingestion of AM at (30 and 60 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that AM is a potentially useful agent for the treatment of breast cancer.
    Matched MeSH terms: Humans
  8. Fulltext α-Mangostin Nanoparticles Cytotoxicity and Cell Death Modalities in Breast Cancer Cell Lines
    Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M
    Molecules, 2021 Aug 24;26(17).
    PMID: 34500560 DOI: 10.3390/molecules26175119
    α-Mangostin (AMG) is a potent anticancer xanthone that was discovered in mangosteen (Garcinia mangostana Linn.). AMG possesses the highest opportunity for chemopreventive and chemotherapeutic therapy. AMG inhibits every step in the process of carcinogenesis. AMG suppressed multiple breast cancer (BC) cell proliferation and apoptosis by decreasing the creation of cancerous compounds. Accumulating BC abnormalities and their associated molecular signaling pathways promotes novel treatment strategies. Chemotherapy is a commonly used treatment; due to the possibility of unpleasant side effects and multidrug resistance, there has been substantial progress in searching for alternative solutions, including the use of plant-derived natural chemicals. Due to the limitations of conventional cancer therapy, nanotechnology provides hope for effective and efficient cancer diagnosis and treatment. Nanotechnology enables the delivery of nanoparticles and increased solubility of drugs and drug targeting, resulting in increased cytotoxicity and cell death during BC treatment. This review summarizes the progress and development of AMG's cytotoxicity and the mechanism of death BC cells. The combination of natural medicine and nanotechnology into a synergistic capital will provide various benefits. This information will aid in the development of AMG nanoparticle preparations and may open up new avenues for discovering an effective BC treatment.
    Matched MeSH terms: Humans
  9. α-Haemoglobin stabilising protein expression is influenced by mean cell haemoglobin and HbF levels in HbE/β-thalassaemia individuals
    Lim WF, Muniandi L, George E, Sathar J, Teh LK, Gan GG, et al.
    Blood Cells Mol. Dis., 2012 Jan 15;48(1):17-21.
    PMID: 22079025 DOI: 10.1016/j.bcmd.2011.10.002
    The alpha haemoglobin stabilising protein (AHSP) acts as a molecular chaperone for α-globin by stabilising nascent α-globin before transferring it to waiting free β-globin chains. Binding of AHSP to α-globin renders α-globin chemically inert whereby preventing it from precipitating and forming reactive oxygen species byproducts. The AHSP has been actively studied in the recent years, particularly in its relation to β-thalassaemia. Studies have shown that AHSP is a modifier in β-thalassaemia mice models. However, this relationship is less established in humans. Studies by some groups showed no correlation between the AHSP haplotypes and the severity of β-thalassaemia, whereas others have shown that certain AHSP haplotype could modify the phenotype of β-thalassaemia intermedia patients. We investigated the expression of AHSP in relation to selected demographic data, full blood count, HPLC results, HbE/β-thalassaemia genotype, Xmn-1 Gγ polymorphism, α-globin, β-globin and γ-globin expression. We found that AHSP expression was significantly correlated to mean cell haemoglobin level, HbF %, α-globin, β-globin and excess α-globin expression. We concluded that AHSP could be a secondary compensatory mechanism in red blood cells to counterbalance the excess α-globin chains in HbE/β-thalassaemia individuals.
    Matched MeSH terms: Humans
  10. α-Glucosidase activity of oleanolic acid and its oxidative metabolites: DFT and Docking studies
    Anouar el H, Zakaria NS, Alsalme A, Shah SA
    Mini Rev Med Chem, 2015;15(14):1148-58.
    PMID: 26205959
    A natural pentacyclic triterpenoid oleanolic acid 1 and its biotransformed metabolites 2-3 are potential α-glucosidase inhibitors. To elucidate the inhibitory mechanism of compounds 1, 2 and 3 against α-glucosidase, we calculated (i) their electronic and optical properties using DFT and TD-DFT at the B3LYP/6-31G(d) level in gas and IEF-PCM solvent; and (ii) their binding energies to α-glucosidase via docking study. DFT results showed that the α-glucosidase inhibtion is mainly depend on the polarity parameters of the studied compounds. Docking results revealed that the activity increased with binding energies (i.e. the stability of ligand-receptor complex). The specroscopic data of oleanolic acid 1 and its metabolites 2 and 3 are well predicetd for 13C NMR chemical shifts (R2=99%) and 1H NMR chemical shifts (R2=90%); and for (ii) UV/vis spectra. The assignments and interpretation of NMR chemical shifts and bathochromic shift of λMAX absorption bands are discussed.
    Matched MeSH terms: Humans
  11. Fulltext α-Amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory effects of Melicope latifolia bark extracts and identification of bioactive constituents using in vitro and in silico approaches
    Quek A, Kassim NK, Lim PC, Tan DC, Mohammad Latif MA, Ismail A, et al.
    Pharm Biol, 2021 Dec;59(1):964-973.
    PMID: 34347568 DOI: 10.1080/13880209.2021.1948065
    CONTEXT: Melicope latifolia (DC.) T. G. Hartley (Rutaceae) was reported to contain various phytochemicals including coumarins, flavonoids, and acetophenones.

    OBJECTIVE: This study investigates the antidiabetic and antioxidant effects of M. latifolia bark extracts, fractions, and isolated constituents.

    MATERIALS AND METHODS: Melicope latifolia extracts (hexane, chloroform, and methanol), fractions, and isolated constituents with varying concentrations (0.078-10 mg/mL) were subjected to in vitro α-amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory assay. Molecular docking was performed to study the binding mechanism of active compounds towards α-amylase and DPP-4 enzymes. The antioxidant activity of M. latifolia fractions and compounds were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and β-carotene bleaching assays.

    RESULTS: Melicope latifolia chloroform extract showed the highest antidiabetic activity (α-amylase IC50: 1464.32 μg/mL; DPP-4 IC50: 221.58 μg/mL). Fractionation of chloroform extract yielded four major fractions (CF1-CF4) whereby CF3 showed the highest antidiabetic activity (α-amylase IC50: 397.68 μg/mL; DPP-4 IC50: 37.16 μg/mL) and resulted in β-sitosterol (1), halfordin (2), methyl p-coumarate (3), and protocatechuic acid (4). Isolation of compounds 2-4 from the species and their DPP-4 inhibitory were reported for the first time. Compound 2 showed the highest α-amylase (IC50: 197.53 μM) and β-carotene (88.48%) inhibition, and formed the highest number of molecular interactions with critical amino acid residues of α-amylase. The highest DPP-4 inhibition was exhibited by compound 3 (IC50: 911.44 μM).

    DISCUSSION AND CONCLUSIONS: The in vitro and in silico analyses indicated the potential of M. latifolia as an alternative source of α-amylase and DPP-4 inhibitors. Further pharmacological studies on the compounds are recommended.

    Matched MeSH terms: Humans
  12. von Willebrand disease: Diagnosis and treatment, treatment of women, and genomic approach to diagnosis
    Laffan M, Sathar J, Johnsen JM
    Haemophilia, 2021 Feb;27 Suppl 3:66-74.
    PMID: 32578345 DOI: 10.1111/hae.14050
    von Willebrand disease (VWD) is the most common inherited bleeding disorder. VWD is caused by deficiencies in von Willebrand factor (VWF), a critical adhesive haemostatic protein. This review provides an overview of VWD diagnosis and treatment, special considerations in treating women with VWD, and current genomic approaches to VWD. For diagnosis and treatment in VWD, an accurate diagnosis is critical to providing effective treatments, determining appropriate laboratory monitoring and for counselling the patient and family. Diagnosis of VWD begins with the clinical assessment for the bleeding phenotype, which is usually characterized by mucocutaneous and provoked bleeding. The diagnosis of VWD is then made by laboratory investigation. Multiple assays are used to assess VWF levels and functions. The mainstays of VWD treatment are tailored by VWD type and symptoms, and can include antifibrinolytic treatment, desmopressin and VWF replacement treatment. Women with VWD are also at risk for excessive uterine bleeding, such as with menses and childbirth. In addition to standard VWD treatments, heavy menstrual bleeding can be treated with hormones. Interdisciplinary management of childbirth and prophylaxis in the postpartum period are needed to reduce the risk of postpartum haemorrhage. Genomic approaches to VWD can inform VWD diagnosis, treatment, test assay selection, reproductive planning and family counselling. Most VWD patients have an identifiable VWF gene DNA variant. Next-generation sequencing is rapidly being adopted to provide more comprehensive VWF sequence information for patients with known or suspected VWD.
    Matched MeSH terms: Humans
  13. Fulltext von Willebrand Factor Propeptide: A Potential Disease Biomarker Not Affected by ABO Blood Groups
    Marianor M, Zaidah AW, Maraina ChC
    Biomark Insights, 2015;10:75-9.
    PMID: 26339184 DOI: 10.4137/BMI.S24353
    Epidemiological studies have shown that vascular-related disorders are associated with high von Willebrand factor antigen (VWF:Ag) and VWF propeptide (VWFpp). VWFpp is secreted together with VWF:Ag upon endothelial cell activation, hence it could be a potential biomarker. This study was conducted to compare between VWF:Ag and VWFpp levels among 30 healthy individuals and 42 patients with high levels of VWF:Ag in different medical conditions and ABO blood groups. VWFpp levels were strongly correlated with VWF:Ag. VWF:Ag and VWFpp levels were significantly increased in patients compared to healthy individuals. VWFpp is not affected by ABO blood group in both healthy individual and patient groups unlike VWF:Ag. As expected, this study showed that VWFpp levels increased in parallel with VWF:Ag levels in patients with diseases associated with endothelial activation. VWFpp though nonspecific is a potential biomarker reflecting underlying pathophysiological changes in various medical conditions with an additional advantage of not being influenced by ABO blood groups.
    Matched MeSH terms: Humans
  14. Fulltext trans-Di-chlorido-bis-(dimethyl sulfoxide-κO)bis-(4-fluoro-benzyl-κC(1))tin(IV): crystal structure and Hirshfeld surface analysis
    Amin NABM, Hussen RSD, Lee SM, Halcovitch NR, Jotani MM, Tiekink ERT
    Acta Crystallogr E Crystallogr Commun, 2017 May 01;73(Pt 5):667-672.
    PMID: 28529772 DOI: 10.1107/S2056989017005072
    The Sn(IV) atom in the title diorganotin compound, [Sn(C7H6F)2Cl2(C2H6OS)2], is located on a centre of inversion, resulting in the C2Cl2O2 donor set having an all-trans disposition of like atoms. The coordination geometry approximates an octa-hedron. The crystal features C-H⋯F, C-H⋯Cl and C-H⋯π inter-actions, giving rise to a three-dimensional network. The respective influences of the Cl⋯H/H⋯Cl and F⋯H/H⋯F contacts to the mol-ecular packing are clearly evident from the analysis of the Hirshfeld surface.
    Matched MeSH terms: Humans
  15. trans-Cinnamic Acid Conjugated Gold Nanoparticles as Potent Therapeutics against Brain-Eating Amoeba Naegleria fowleri
    Rajendran K, Anwar A, Khan NA, Shah MR, Siddiqui R
    ACS Chem Neurosci, 2019 06 19;10(6):2692-2696.
    PMID: 30970208 DOI: 10.1021/acschemneuro.9b00111
    Primary amoebic meningoencephalitis (PAM), a deadly brain infection, is caused by brain-eating amoeba Naegleria fowleri. The current first line of treatment against PAM is a mixture of amphotericin B, rifampin, and miltefosine. Since, no single effective drug has been developed so far, the mortality rate is above 95%. Moreover, severe adverse side effects are associated with these drugs. Nanotechnology has provided several advances in biomedical applications especially in drug delivery and diagnosis. Herein, for the first time we report antiamoebic properties of cinnamic acid (CA) and gold nanoparticles conjugated with CA (CA-AuNPs) against N. fowleri. CA-AuNPs were successfully synthesized by sodium borohydride reduction of tetrachloroauric acid. Size and morphology were determined by atomic force microscopy (AFM) while the surface plasmon resonance band was analyzed by ultraviolet-visible (UV-vis) spectrophotometry for the characterization of the nanoparticles. Amoebicidal and cytopathogenicity (host cell cytotoxicity) assays revealed that both CA and CA-AuNPs displayed significant anti- N. fowleri properties ( P < 0.05), whereas nanoparticles conjugation further enhanced the anti- N. fowleri effects of CA. This study established a potential drug lead, while CA-AuNPs appear to be promising candidate for drug discovery against PAM.
    Matched MeSH terms: Humans
  16. Fulltext sn-2 Hypothesis: a Review of the Effects of Palm Oil on Blood Lipid Levels
    Sin Teh S, Ong ASH, Choo YM, Mah SH
    J Oleo Sci, 2018;67(6):697-706.
    PMID: 29863090 DOI: 10.5650/jos.ess18009
    Saturated fats are commonly claimed to raise human blood cholesterols and contribute to cardiovascular disease. Previous literature data were highlighted that although palm oil is 50% saturated, it does not behave like a saturated fat. Human trials were conducted to compare the effects on serum cholesterol levels given by palm olein and monounsaturated oils. It was postulated that saturation/unsaturation of the fatty acids situated at sn-2 positions of triglycerides in the fat molecules determine the induced blood lipid levels but not the overall saturation of oils. The results showed that the lipid parameters (LDL and HDL) effects induced by these oils are similar with no significant differences. This study provides concrete evidence that the unsaturation levels of these oils at sn-2 position of TG are similar (90-100%) which are claimed to be responsible for the lipid parameters. In conclusion, the public negative perception on believing that the overall saturation of oils is detrimental to health should be corrected because in fact the unsaturation at sn-2 positions of the saturated vegetable fat such as palm olein and cocoa butter make them behave like mono-unsaturated oils, unlike saturated animal fats that possess a high content of saturated fatty acids at sn-2 position.
    Matched MeSH terms: Humans
  17. siRNAs targeting multidrug transporter genes sensitise breast tumour to doxorubicin in a syngeneic mouse model
    Tiash S, Chowdhury EH
    J Drug Target, 2019 03;27(3):325-337.
    PMID: 30221549 DOI: 10.1080/1061186X.2018.1525388
    Chemotherapy, the commonly favoured approach to treat cancer is frequently associated with treatment failure and recurrence of disease as a result of development of multidrug resistance (MDR) with concomitant over-expression of drug efflux proteins on cancer cells. One of the most widely used drugs, doxorubicin (Dox) is a substrate of three different ATP-binding cassette (ABC) transporters, namely, ABCB1, ABCG2 and ABCC1, predominantly contributing to MDR phenotype in cancer. To silence these transporter-coding genes and thus enhance the therapeutic efficacy of Dox, pH-sensitive carbonate apatite (CA) nanoparticles (NPs) were employed as a carrier system to co-deliver siRNAs against these genes and Dox in breast cancer cells and in a syngeneic breast cancer mouse model. siRNAs and Dox were complexed with NPs by incubation at 37 °C and used to treat cancer cell lines to check cell viability and caspase-mediated signal. 4T1 cells-induced breast cancer mouse model was used for treatment with the complex to confirm their action in tumour regression. Smaller (∼200 nm) and less polydisperse NPs that were taken up more effectively by tumour tissue could enhance Dox chemosensitivity, significantly reducing the tumour size in a very low dose of Dox (0.34 mg/kg), in contrast to the limited effect observed in breast cancer cell lines. The study thus proposes that simultaneous delivery of siRNAs against transporter genes and Dox with the help of CA NPs could be a potential therapeutic intervention in effectively treating MDR breast cancer.
    Matched MeSH terms: Humans
  18. siRNA-mediated inhibition of survivin gene enhances the anti-cancer effect of etoposide in U-937 acute myeloid leukemia cells
    Jafarlou M, Baradaran B, Shanehbandi D, Saedi TA, Jafarlou V, Ismail P, et al.
    Cell Mol Biol (Noisy-le-grand), 2016 May 30;62(6):44-9.
    PMID: 27262801
    Acute myeloid leukemia (AML) is one of the most frequent types of leukemia which mostly affects adult people. Resistance to therapeutic drugs is considered as a major clinical concern resulting in a weaker response to chemotherapy, disease relapse and decreased survival rate. Survivin, a member of Inhibitor of Apoptosis Proteins (IAPs), is associated with drug resistance and inhibition of apoptotic mechanisms in numerous hematological malignancies. In the present study, we examined the combined effect of etoposide and siRNA-mediated silencing of survivin on U-937 acute myeloid leukemia cells. The AML cells were transfected with survivin specific siRNA and gene knockdown was confirmed by quantitative real time PCR and western blotting. Subsequently, U-937 cells were assessed for response to etoposide treatment and apoptosis rate was measured with flowcytometery. The cytotoxic effects in siRNA-etoposide group were measured and compared to etoposide single therapy group. Survivin siRNA effectively knocked down the mRNA and protein levels of survivin, which led to lower cell proliferation and enhanced apoptosis. Furthermore, combined treatment of etoposide and survivin siRNA synergistically increased the cell toxic effects of etoposide and its ability to induce apoptosis.
    Matched MeSH terms: Humans
  19. siRNA Therapy, Challenges and Underlying Perspectives of Dendrimer as Delivery Vector
    Tekade RK, Maheshwari RG, Sharma PA, Tekade M, Chauhan AS
    Curr Pharm Des, 2015;21(31):4614-36.
    PMID: 26486147
    siRNA technology presents a helpful means of gene silencing in mammalian cells. Advancement in the field includes enhanced attentiveness in the characterization of target and off-target effects employing suitable controls and gene expression microarrays. These will permit expansion in the measurement of single and multiple target combinations and also permit comprehensive efforts to understand mammalian cell processes. Another fact is that the delivery of siRNA requires the creation of a nanoparticulate vector with controlled structural geometry and surface modalities inside the targeted cells. On the other hand, dendrimers represent the class of carrier system where massive control over size, shape and physicochemical properties makes this delivery vector exceptional and favorable in genetic transfection applications. The siRNA therapeutics may be incorporated inside the geometry of the density controlled dendrimers with the option of engineering the structure to the specific needs of the genetic material and its indication. The existing reports on the siRNA carrying and deliverance potential of dendrimers clearly suggest the significance of this novel class of polymeric architecture and certainly elevate the futuristic use of this highly branched vector as genetic material delivery system.
    Matched MeSH terms: Humans
  20. Fulltext scFv antibody: principles and clinical application
    Ahmad ZA, Yeap SK, Ali AM, Ho WY, Alitheen NB, Hamid M
    Clin. Dev. Immunol., 2012;2012:980250.
    PMID: 22474489 DOI: 10.1155/2012/980250
    To date, generation of single-chain fragment variable (scFv) has become an established technique used to produce a completely functional antigen-binding fragment in bacterial systems. The advances in antibody engineering have now facilitated a more efficient and generally applicable method to produce Fv fragments. Basically, scFv antibodies produced from phage display can be genetically fused to the marker proteins, such as fluorescent proteins or alkaline phosphatase. These bifunctional proteins having both antigen-binding capacity and marker activity can be obtained from transformed bacteria and used for one-step immunodetection of biological agents. Alternatively, antibody fragments could also be applied in the construction of immunotoxins, therapeutic gene delivery, and anticancer intrabodies for therapeutic purposes. This paper provides an overview of the current studies on the principle, generation, and application of scFv. The potential of scFv in breast cancer research is also discussed in this paper.
    Matched MeSH terms: Humans
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